Treatment of Conjunctival Mucosa-Associated Lymphoid Tissue Lymphoma With Intralesional Injection of Interferon Alfa-2b

Conjunctival mucosa-associated lymphoid tissue (MALT) lymphomas are typically localized, low-grade tumors that differ histologically from other forms of primary extranodal non-Hodgkin lymphomas. Patients with conjunctival MALT lymphoma have been cared for with radiation, chemotherapy, surgical excision, cryotherapy, and even observation alone. To our knowledge, this is only the third report of conjunctival MALT lymphoma treated with local injection of interferon alfa-2b (IFN-α-2b)^1,2 and the first to appear in the North American ophthalmic literature.

A 21-year-old male student had a 2-month history of a painless, progressively enlarging mass on his right eye. Findings from anterior segment examination revealed a large salmon-colored lesion involving the right nasal conjunctiva, caruncle, and superior and inferior fornices (Figure 1). His uncorrected visual acuity was 20/20 OU and findings from the remainder of the ocular examination were unremarkable. The patient was tentatively diagnosed as having a conjunctival lymphoid neoplasm, pending biopsy and orbital imaging. He acknowledged a 40-lb weight loss during a 2-year period and moderate fatigue of recent onset. He denied having fever, chills, night sweats, other known masses, and risk factors associated with human immunodeficiency virus infection. He was otherwise healthy with no family history of hematological malignancy. Findings from physical examination demonstrated a thin man without evidence of lymphadenopathy or hepatosplenomegaly. A conjunctival biopsy was performed. Sections of the conjunctival biopsy specimen showed a diffuse, small, cleaved lymphocytic infiltrate with occasional cells percolating into the epithelial layer (Figure 2). Immunoperoxidase stains were positive for CD20 (a B-cell marker) and negative for CD3 (a T-cell marker). Findings from flow cytometry demonstrated κ light chain restriction (80%) and were positive for CD19 (a B-cell marker) (86%). A clonal rearrangement of the heavy chain, indicative of a clonal lymphoproliferative cell population, was demonstrated by polymerase chain reaction. No evidence of circulating lymphoma cells was found in either the blood or bone marrow by morphology, flow cytometry, or polymerase chain reaction. A computed tomographic scan of his head did not show orbital extension or intracranial abnormality. A computed tomographic scan of the chest, abdomen, and pelvis showed no abnormalities. We elected to treat this patient with an intralesional injection of 1,000,000 U of IFN-α-2b, administered 3 times weekly for a total of 12 doses. One month later, at the conclusion of treatment, the mass was considerably smaller. By 3 months, despite no additional therapeutic intervention, the conjunctival mass was undetectable (Figure 1). There is no evidence of recurrence after 3 additional months of follow-up, and the patient is otherwise healthy.

Lymphoid neoplasms of the conjunctiva are usually treated with radiotherapy. Bessell et al³ report no recurrence and a low rate of ocular morbidity in 115 patients receiving 30 or 40 Gy during 3 or 4 weeks; 8 (7%) developed radiation-induced cataracts, and 5 (4%) experienced disorders of ocular lubrication, despite shielding of the cornea and lens. Interferon alfa-2b is a glycoprotein produced by leukocytes possessing antiviral, immunoregulatory, and antitumor activity. The mechanisms responsible for its antitumor effects may include modulation of oncogenes and up-regulation of tumor cell surface antigens. As a single agent, its role seems limited to the treatment of low-grade lymphomas.⁴ Adverse effects include fevers, chills, and myalgias. Fatigue, anorexia, and weight loss may occur with protracted use. Complete remission was achieved in all 5 previously described patients with conjunctival lymphoma treated with local injection of IFN-α-2b.^1,2 Adverse effects, if any, were not discussed. Our patient experienced transient headaches and nausea following the first 3 injections. The injection itself caused subconjunctival hemorrhage twice. The absence of vision-threatening complications and demonstrated efficacy, in this case, may warrant further consideration of the role of intralesional IFN-α-2b injection for treating conjunctival MALT lymphoma. Long-term follow-up of this and other cases is needed.

Corresponding author: Kevin Lachapelle, MD, Department of Ophthalmology, Queen's University, Kingston, Ontario, Canada K7L 3N6.